A study of angiogenesis and oral cancer stem-like cells

Autor: Wei-TingKang, 康瑋庭
Rok vydání: 2013
Druh dokumentu: 學位論文 ; thesis
Popis: 101
Oral squamous cell carcinoma (OSCC), the most common cancer in the oral and maxillofacial region, is the sixth most prevalent type of malignancy worldwide and account for approximately 8% to 10% of all cancers in Asia. Some studies indicate that tumor sphere has more cancer stem-like (CSCs) cells. Angiogenesis is the propelling force for tumor growth and metastasis. Some cancer patients also accompany drug resistance during treatment, so they have poor prognosis after chemotherapy treatment. A portion of the patients can not be completely cured due to cancer metastasis. Therefore, many researchers highly suspect that cancer stem-like cells and angiogenesis may be the main reasons for this phenomenon. First, we compared human tongue squamous cell carcinoma (SAS) tumor sphere and monolayer for expression of stem cell genes and related proteins, including CD133, Nanog, ALDH1A1 and Oct4, using quantitative RT-PCR, western blotting, and immunostaining to analyze these stem cell markers expression in tumor sphere. Next, we utilized angiogenesis PCR array to identify up-regulated angiogenic factors. We also confirmed the findings using real-time PCR on cell-sorted CD133+ cells to reconfirm the data. The levels of CD133, Nanog, ALDH1A1 and Oct4 were up-regulated in tumor sphere compared with monolayer based on quantitative RT-PCR, western blotting and immunostaining. We demonstrated tumor sphere contained more cancer stem-like cell. The data of angiogenesis PCR array identified up-regulation of several angiogenic factors, including CXCL10 (C-X-C motif Chemokine 10), CXCL3 (C-X-C motif Chemokine 3), IL8 (Interleukin 8) and TNF (Tumor nerosis factor). Most of them are chemotactic factors. Cell sorting for CD133+ cells also confirm CXCL3, IL8 and TNF were more expressed in CD133+ cells. We were also examined endothelium cell marker Factor VIII and found that it was more expressed in CD133+ cells. Our analysis indicated that tumor sphere have cancer stem-like cell characteristics. We identified some upregulated angiogenic factors (chemotactic factors) in cancer stem-like cells. The results may help to develop new cancer therapies.
Databáze: Networked Digital Library of Theses & Dissertations